Homocysteinic acid causes oxidative stress in lymphocytes by potentiating toxic effect of NMDA

Short-term incubation of lymphocytes with homocysteine or its oxidation product homocysteinic acid increased the formation of reactive oxygen species and cell necrosis (in case of homocysteinic acid). Effective concentration of homocysteine and homocysteinic acid (500 mu M) significantly surpassed the level observed during hyperhomocysteinemia. The addition of homocysteinic acid in a nontoxic concentration of 100 mu M potentiated the toxic effect of NMDA and led to massive cell death. During hyperhomocysteinemia the amount of these metabolites in the blood was much higher than in the brain. Oxidative stress produced by these substances can result from activation of NMDA glutamate receptors that were recently detected on lymphocytes.